Abstract
Background and Aim: Negatively charged nanoliposomes have a strong attraction towards plasma lipoprotein particles and can thereby regulate lipid metabolism. Here, the impact of such nanoliposomes on dyslipidaemia and progression of atherosclerosis was investigated in a rabbit model.
Methods: Two sets of negatively-charged nanoliposome formulations including [Hydrogenated Soy Phosphatidylcholine (HSPC)/1,2-distearoyl-sn-glycero-3- phosphoglycerol (DSPG)] and [1,2- Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC)/1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPG)/Cholesterol] were evaluated. Rabbits fed a high-cholesterol diet were randomly divided into 3 groups (n=5/group) intravenously administrated with HSPC/DSPG formulation (DSPG group; 100 mmol/kg), DMPC/DMPG formulation (DMPG group; 100 mmol/kg), or the normal saline (control group; 0.9% NaCl) over a 4-week period. The atherosclerotic lesions of the aortic arch wall were studied using haematoxylin and eosin staining.
Results: Both DSPG and DMPG nanoliposome formulations showed a nano-sized range in diameter with a negatively-charged surface and a polydispersity index of <0.1. After 4 weeks administration, the nanoliposome formulations decreased triglycerides (-62±3% [DSPG group] and -58±2% [DMPG group]), total cholesterol (-58±9% [DSPG group] and -37±5% [DMPG group]), and lowdensity lipoprotein cholesterol (-64±6% [DSPG group] and -53±10% [DMPG group]) levels, and increased high-density lipoprotein cholesterol (+67±28% [DSPG group] and +35±19% [DMPG group]) levels compared with the controls. The nanoliposomes showed a significant decrease in the severity of atherosclerotic lesions: mean values of the intima to media ratio in DMPG (0.96±0.1 fold) and DSPG (0.54±0.02 fold) groups were found to be significantly lower than that in the control (1.2±0.2 fold) group (p<0.05).
Conclusion: Anionic nanoliposomes containing [HSPC/DSPG] and [DMPC/DMPG] correct dyslipidaemia and inhibit the progression of atherosclerosis.
Keywords: Atherosclerosis, anionic nanoliposome, dyslipidaemia, phosphoglycerol, nanoparticles, lipoprotein.
Graphical Abstract
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.676890] [PMID: 17938300]
[http://dx.doi.org/10.1093/eurheartj/ehz962] [PMID: 32052833]
[http://dx.doi.org/10.1016/j.plipres.2015.08.003] [PMID: 26416579]
[http://dx.doi.org/10.5114/aoms.2020.94655] [PMID: 32399094]
[http://dx.doi.org/10.1160/th15-08-0620] [PMID: 26632869]
[http://dx.doi.org/10.1038/srep09902] [PMID: 25970700]
[http://dx.doi.org/10.1161/CIR.0b013e3182160726] [PMID: 21502576]
[http://dx.doi.org/10.1001/jama.298.3.299] [PMID: 17635890]
[http://dx.doi.org/10.1056/NEJMoa1107579] [PMID: 22085343]
[http://dx.doi.org/10.1523/JNEUROSCI.3990-12.2013] [PMID: 23486965]
[http://dx.doi.org/10.1007/s11883-009-0080-0] [PMID: 20425274]
[http://dx.doi.org/10.1016/j.colsurfb.2015.03.012] [PMID: 25829129]
[http://dx.doi.org/10.1002/jcp.26610] [PMID: 29741759]
[http://dx.doi.org/10.1016/j.colsurfb.2014.07.045] [PMID: 25139293]
[http://dx.doi.org/10.4068/cmj.2021.57.1.27] [PMID: 33537216]
[http://dx.doi.org/10.1038/nrd1632] [PMID: 15688077]
[http://dx.doi.org/10.1126/science.3513311] [PMID: 3513311]
[http://dx.doi.org/10.1002/jps.10075] [PMID: 11977099]
[http://dx.doi.org/10.1023/A:1010971808006] [PMID: 11496949]
[http://dx.doi.org/10.1016/S0005-2736(98)00102-3] [PMID: 9733956]
[http://dx.doi.org/10.1074/jbc.273.52.35355] [PMID: 9857078]
[http://dx.doi.org/10.1074/jbc.270.27.16221] [PMID: 7541795]
[http://dx.doi.org/10.1016/0005-2760(95)00088-T] [PMID: 7647101]
[http://dx.doi.org/10.1016/j.pharmthera.2014.09.009] [PMID: 25277507]
[http://dx.doi.org/10.1258/002367797780600297] [PMID: 9121105]
[http://dx.doi.org/10.1258/002367796780739871] [PMID: 8938617]
[http://dx.doi.org/10.1067/mva.2002.121756] [PMID: 11877706]
[http://dx.doi.org/10.1038/nmeth.2089] [PMID: 22930834]
[http://dx.doi.org/10.1016/S0009-9120(01)00263-6] [PMID: 11738396]
[http://dx.doi.org/10.1186/1476-511X-11-132] [PMID: 23046637]
[PMID: 26793631]
[http://dx.doi.org/10.1016/0305-0491(82)90252-8] [PMID: 7060347]
[http://dx.doi.org/10.1016/S0022-2275(20)33428-3] [PMID: 10946008]
[http://dx.doi.org/10.1194/jlr.M300062-JLR200] [PMID: 12700341]
[http://dx.doi.org/10.1194/jlr.M400438-JLR200] [PMID: 15576836]
[http://dx.doi.org/10.1016/S0022-2275(20)39140-9] [PMID: 8827528]
[http://dx.doi.org/10.1016/j.chemphyslip.2008.04.006] [PMID: 18502203]
[http://dx.doi.org/10.1139/O07-137] [PMID: 18059528]
[http://dx.doi.org/10.1016/0005-2760(90)90291-5] [PMID: 2317527]
[http://dx.doi.org/10.3109/08982104.2013.863208] [PMID: 24443972]
[http://dx.doi.org/10.1172/JCI9794] [PMID: 11238557]
[http://dx.doi.org/10.1016/j.cmet.2005.01.002] [PMID: 16054053]
[http://dx.doi.org/10.1073/pnas.97.8.4245] [PMID: 10760292]
[http://dx.doi.org/10.1073/pnas.200367697] [PMID: 11035776]
[http://dx.doi.org/10.1038/nm1102-1243] [PMID: 12411951]